Chemistry

Toxicity

Oxygen

Drug

Hypoxia (environmental)

Neuroscience

Organic chemistry

Myocardial infarction

Biology

Infarction

Cardiology

Organoid

Cardiac function curve

Internal medicine

Heart failure

Cardiotoxicity

Pharmacology

Medicine

Nature Biomedical Engineering

Environmental factors are the largest contributors to cardiovascular disease. Here we show that cardiac organoids that incorporate an oxygen-diffusion gradient and that are stimulated with the neurotransmitter noradrenaline model the structure of the human heart after myocardial infarction (by mimicking the infarcted, border and remote zones), and recapitulate hallmarks of myocardial infarction (in particular, pathological metabolic shifts, fibrosis and calcium handling) at the transcriptomic, structural and functional levels. We also show that the organoids can model hypoxia-enhanced doxorubicin cardiotoxicity. Human organoids that model diseases with non-genetic pathological factors could help with drug screening and development. Cardiac organoids incorporating an oxygen-diffusion gradient and stimulated with the neurotransmitter noradrenaline can model the structure and function of the human heart after myocardial infarction.

Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity